The proposed studies are a continuation of investigations underway and are directed toward determining the optimal culture and isolation conditions required for the maximal production of insulin receptors on skeletal muscle cells in culture and the biological consequences of the insulin receptors on hexose and amino acid uptake and RNA synthesis. Having established the above, we propose to determine whether the insulin receptor-effector systems exist in a stimulated state and thus are not responsive to added insulin or whether the insulin receptors cannot react properly with potentially functional effector systems to elicit an insulin response. This research will hopefully provide important information on the regulation of insulin action and give some insight to disease states showing insulin resistance by the patient. The approach uses insulin binding studies, determinations of metabolite uptake and cellular synthesis of RNA. Several oxidizing, reducing and sulfhydryl blocking agents will be used to analyze the regulatory aspects of insulin action.